GENE-THERAPY IN PEDIATRIC ONCOLOGY

An increased understanding of the molecular mechanisms of cancer and t he ability to introduce exogenous genes into mammalian cells has led t o the development of oncologic treatment strategies based upon gene tr ansfer. Preclinical animal models have suggested a variety of approach es which are now being tested in pediatric trials. Studies using marke r genes to trace cell origin have already generated important informat ion regarding autologous bone marrow transplantation for pediatric can cers. A variety of therapeutic genes are also being clinically tested. Trials are underway to determine if introduction of immunostimulatory genes into cancer cells can be used to enhance host antitumor immunit y. Treatment of primary brain tumors with insertion of drug sensitizat ion genes is a promising new therapy that is also being clinically eva luated. Other strategies such as insertion of drug resistance genes in to hematopoietic cells, anti-oncogene therapy, and tumor suppressor ge ne replacement are being tested in adults and may find use in pediatri c cancer treatment. Although gene transfer offers promising new approa ches for the therapy of pediatric cancer, many technical problems rema in which limit efficacy and widespread use. Further basic research in the molecular biology of cancer and in vector development will be requ ired to realize the full potential of gene therapy strategies.